The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Targeting CDK4/6 in patients with cancer
Open accessAbstract
The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway controls cell cycle progression by regulating the G1-S checkpoint. Dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway results in increased proliferation, and is frequently observed in many types of cancer. Pathway activation can occur through a variety of mechanisms, including gene amplification or rearrangement, loss of negative regulators, epigenetic alterations, and point mutations in key pathway components. Due to the importance of CDK4/6 activity in cancer cells, CDK4/6 inhibitors have emerged as promising candidates for cancer treatment. Moreover, combination of a CDK4/6 inhibitor with other targeted therapies may help overcome acquired or de novo treatment resistance. Ongoing studies include combinations of CDK4/6 inhibitors with endocrine therapy and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors for hormone receptor-positive (HR+) breast cancers, and with selective RAF and MEK inhibitors for tumors with alterations in the mitogen activated protein kinase (MAPK) pathway such as melanoma. In particular, the combination of CDK4/6 inhibitors with endocrine therapy, such as palbociclib's recent first-line approval in combination with letrozole, is expected to transform the treatment of HR+ breast cancer. Currently, three selective CDK4/6 inhibitors have been approved or are in late-stage development: palbociclib (PD-0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Here we describe the current preclinical and clinical data for these novel agents and discuss combination strategies with other agents for the treatment of cancer.
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Citations
Cites
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Cell cycle, CDKs and cancer: a changing paradigm
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“Increased cyclin D-CDK4/6 activity, which promotes phosphorylation of Rb, can occur through several mechanisms, including overexpression of D-type cyclins, mutation or amplification of CDK4/6, or loss of cyclin D-CDK4/6 negative regulators such as p16 [1–3], and ultimately leads to cancer cell growth.”
BackgroundA landscape of driver mutations in melanoma
Hodis, E., Watson, I. R., Kryukov, G. V., Arold, S. T., Imielinski, M., Theurillat, J.-P., Nickerson, E., Auclair, D., Li, L., Place, C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.024 · Cited by 2,610
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“models [5,34–38,42,45,89] MCL, myeloma, breast, lung, brain,”
BackgroundGermline mutations in the p16INK4a binding domain of CDK4 in familial melanoma
Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., Walker, G. J., Hayward, N., & Dracopoli, N. C. (1996) · Nature Genetics · doi:10.1038/ng0196-97 · Cited by 818 · cited 1×
“CDK4 R24 mutations were first characterized in familial melanoma [19], and were identified in 2.”
BackgroundAnders, L., Ke, N., Hydbring, P., Choi, Y. J., Widlund, H. R., Chick, J. M., Zhai, H., Vidal, M., Gygi, S. P., Braun, P., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.001 · Cited by 543
Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma
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Cited by
Ribociclib as first-line therapy for HR-positive, advanced breast cancer
Hortobagyi, G. N., Stemmer, S. M., Burris, H. A., Yap, Y.-S., Sonke, G. S., Paluch-Shimon, S., Campone, M., Blackwell, K. L., André, F., Winer, E. P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1609709 · Cited by 2,039
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
Ricketts, C. J., De Cubas, A. A., Fan, H., Smith, C. C., Lang, M., Reznik, E., Bowlby, R., Gibb, E. A., Akbani, R., Beroukhim, R., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.032 · Cited by 734
Genome-Informed Targeted Therapy for Osteosarcoma
Sayles, L. C., Breese, M. R., Koehne, A. L., Leung, S. G., Lee, A. G., Liu, H.-Y., Spillinger, A., Shah, A. T., Tanasa, B., Straessler, K., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1152 · Cited by 452
“Genome-Informed Targeting of CDK4 CDK4 is a cyclin-dependent kinase that regulates cell-cycle progression during G1–S and is amplified in a variety of cancers including breast, head and neck, and lung (37).”
BackgroundMolecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review
Pandey, K., An, H., Kim, S. K., Lee, S. A., Kim, S., Lim, S. M., Kim, G. M., Sohn, J., & Moon, Y. W. (2019) · International Journal of Cancer · doi:10.1002/ijc.32020 · Cited by 361
Metadata
- Authors
- Hamilton, E., & Infante, J. R.
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 45
- Pages
- 129-138
- ISSN
- 0305-7372 (ISSN-L)
- OpenAlex
- W2295971206
- Cited by
- 481
- References
- 22
- FWCI
- 34.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
